tbuckley/cabot-search huggingface dataset:
Abstract 10209: The Effect of the Dual SGLT1 and 2 Inhibitor Sotagliflozin on Cardiovascular Mortality and Hospital Readmission Rates for Heart Failure at 30 and 90 Days Post Discharge in Patients With Type 2 Diabetes Hospitalized for Worsening Heart Failure in the SOLOIST-WHF Trial
Authors: Bertram Pitt, Deepak L Bhatt, Michael Szarek, Franklin Sun, Michael J Davies, Philippe G Steg
Journal: Circulation (2022)

Introduction: SGLT inhibitors demonstrate reductions in CV mortality and HHF in patients with diabetes and chronic HF. Despite therapy, patients hospitalized for worsening HF (WHF) are at high risk of death or readmission. Hypothesis: The SOLOIST-WHF trial admitted patients for their index WHF event and initiated randomized therapy during hospitalization. This study evaluated the effect of the SGLT1 and 2 inhibitor sotagliflozin on 30- and 90-day CV death and HF readmission rates after discharge. Methods: Of 1222 randomized patients with T2D, 86% were admitted for their index WHF event. Of them, 46% (n = 563) started study drug prior to or at discharge. In post hoc exploratory analyses, CV death and HF readmission (HHF or urgent visits for HF) rates were determined 30- or 90-days post discharge. Comparisons were done by Cochran-Mantel-Haenszel test stratified by region and baseline LVEF (&lt;50%, ≥50%). Results: Treatment with sotagliflozin showed significant relative risk reduction of &gt;50% for readmission for non-fatal HF-related events or the composite of CV death and readmission for HF-related events within 30 or 90 days of discharge vs placebo (Table 1). The sotagliflozin safety profile in those windows was generally consistent with the overall study duration. Incidence of adverse events (AEs) and serious AEs was similar between groups. Increased incidence of diarrhea and volume-related AEs was noted with sotagliflozin. No appreciable eGFR change from baseline occurred at 30 days, but there was lower incidence of AEs linked to acute kidney injury with sotagliflozin. Conclusions: Sotagliflozin, given to patients with T2D prior to or at hospital discharge after an episode of WHF, was well tolerated and resulted in a significant &gt;50% reduction in CV mortality or readmission for a HF event at 30 and 90 days post-discharge.
Abstract 10239: Association of Lipoprotein(a) and Hypertension in Primary Prevention of Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Rishi Rikhi, Harpreet Bhatia, Christopher L Schaich, Nicklaus Ashburn, David M Herrington, Michael Y Tsai, Erin D Michos, Parag A Chevli, Sam Tsimikas, Michael D Shapiro
Journal: Circulation (2022)

Introduction: The presence of both dyslipidemia and hypertension is associated with considerable cardiovascular disease (CVD) risk, yet few studies have explored the relationship between elevated lipoprotein(a) (Lp(a)) and hypertension. This study explored the longitudinal relationship of Lp(a) and hypertension to cardiovascular outcomes in a large multiethnic cohort free of baseline CVD. Methods: Individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) (n- 6,674) were grouped as follows: Group 1: Lp(a) &lt; 50 mg/dL and no hypertension; Group 2: Lp(a) ≥ 50 mg/dL and no hypertension; Group 3: Lp(a) &lt; 50 mg/dL and hypertension; and Group 4: Lp(a) ≥ 50 mg/dL and hypertension. Kaplan Meier curves and multivariable Cox proportional hazard models were used to assess the relationship between Lp(a) and hypertension with time to CVD events. Results: The mean follow up time was 13.9 years and there were a total of 809 CVD events. A statistically significant interaction was found between LogLp(a) and hypertension status (p = 0.086). Compared to the reference group (Lp(a) &lt; 50 mg/dL and no hypertension), those with Lp(a) ≥ 50 mg/dL and no hypertension (Group 2) had no increase in risk for CVD events (HR: 1.07; 95% CI: 0.78, 1.46) (Table). However, those with Lp(a) &lt; 50 mg/dL and hypertension (Group 3) or Lp(a) ≥ 50 mg/dL and hypertension (Group 4) demonstrated a statistically significant increase in CVD risk compared to the reference group (HR: 1.66; 95% CI: 1.40, 1.98) and (HR: 2.04; 95% CI: 1.62, 2.59), respectively (Table). Among those with hypertension (Groups 3 and 4), Lp(a) was associated with a significant increase in CVD risk (HR: 1.23; 95% CI: 1.00, 1.51). Conclusion: The present study found a significant interaction between Lp(a) and hypertension. More research is needed to understand the mechanistic link between Lp(a), hypertension, and CVD.
Abstract 10788: Identifying Clinical and Demographic Factors Associated With Sub-Optimal Statin Prescription Rates Following Carotid Endarterectomy
Authors: Michael Eppler, Nikhil Singh, Li Ding, Gregory Magee, Parveen Garg
Journal: Circulation (2022)

Introduction: Statin therapy is under prescribed in patients undergoing carotid endarterectomy (CEA). We determined new statin prescription rates following CEA as well as the demographic, clinical, and procedural characteristics associated with likelihood of new prescription. Methods: A retrospective Vascular Quality Initiative analysis of patients undergoing CEA and not on statin therapy pre-procedure between 2013 to 2021 was performed. Multivariate logistic regression was used to determine patient characteristics associated with new statin therapy. Results: Participants undergoing CEA were predominantly male (61%) and white (90%), with a mean age of 70.6 ± 9.1 years. Of all eligible subjects, 13.2% were not on statin therapy at time of CEA, corresponding to 15,733 procedures. New statin therapy was prescribed following 48% of these procedures, with rates increasing throughout the study period (36.2% in 2013 to 62% in 2021) (Figure). A higher likelihood of new statin prescription was associated with non-white race (Asian vs. White (Relative Risk (RR) 1.13; 95% Confidence Interval (CI) 1.06-1.20); Black vs. White (RR 1.26; 95% CI 1.11-1.43)), diabetes (oral medications vs. no diabetes (RR 1.06; 95% CI 1.02-1.11)), coronary heart disease (RR 1.12; 95% CI 1.08-1.16), prior stroke (RR 1.29; 95% CI 1.22-1.37), TIA (RR 1.07; 95% CI 1.00-1.13), and a non-elective indication (elective vs. emergent (RR 1.39; 95% CI 1.27-1.53)). A lower likelihood of new statin prescription was associated with older age (≥77 vs. ≤65 (RR 0.88; 95% CI 0.84-0.93)), female gender (RR 0.95; 95% CI 0.92-0.99), COPD (RR 0.95; 95% CI 0.91-0.99), and prior carotid revascularization (RR 0.87; 95% CI 0.82-0.92). Conclusions: A significant percentage of patients are not on a statin at the time of CEA, and of those, only 48% are discharged on one. System-wide and provider-focused efforts are needed to identify shortcomings in the introduction of this cardioprotective medication into standard of care.
Abstract 10915: Microvascular Obstruction Identifies a Subgroup of Patients Who Benefit From Intracoronary Stem Cell Delivery Following ST-Elevation Myocardial Infarction
Authors: Sarah J Davidson, JEROME RONCALLI, Daniel Surder, Atul R Chugh, Phillip C Yang, Timothy D Henry, Larissa I Stanberry, Patricia Lemarchand, Jean-Paul Beregi, Roberto Corti, Thomas F Luscher, Jay H Traverse
Journal: Circulation (2022)

Aims: Microvascular obstruction (MVO) following ST-elevation myocardial infarction (STEMI) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction. We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction. Methods and Results: We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs as part of 3 clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot (n=157), the multi-center French BONAMI trial (n=91) and the SWISS-AMI trial (n=108). All patients received 100 - 150 million intracoronary autologous BMCs or placebo / control 3 - 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n=210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n=146) (all p &lt; 0.01) (TABLE). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference = 2.7 %; p &lt; 0.05). Similarly, the changes in left-ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV) were consistent with significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo ( % change; LVEDV = -9.7%; p &lt; 0.05 and LVESVI = -14.7 %; p = 0.006). In contrast, patients without MVO experienced no benefit of BMC administration compared to placebo. Conclusion: The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who may benefit from intracoronary stem cell delivery of BMCs.
Abstract 10957: Six Month Patency of Bioengineered Human Acellular Vessels in a Primate Model of Coronary Artery Bypass Grafting
Authors: Adam R Williams, Joseph Nellis, Sharon McCartney, Sachin Mehta, Mihai V PODGOREANU, Melissa A Daubert, Robert Kirkton, Kevin Nash, Christopher J Rhew, Derek Argotti, Daniel N Regan, Derek Sanderson, Laura Niklason, Alan Kypson
Journal: Circulation (2022)

Introduction: Limitations of coronary artery bypass grafting (CABG) include the availability, quality, and long-term patency of autologous saphenous vein grafts. An “off-the-shelf” human acellular vessel (HAV) bioengineered from banked human vascular cells, decellularized before implantation, and capable of host cellular regeneration may address these issues. Therefore, we assessed early patency and tolerability of a small diameter HAV as a CABG conduit in a baboon surgical model. Methods: Adult male, non-immunosuppressed baboons (n = 3; 30.5 - 37.0 kg) underwent CABG via sternotomy with cardiopulmonary bypass. The right coronary artery (RCA) was ligated and bypassed with a 3.5 mm inner diameter HAV. Intraoperative blood flow was determined by transit-time flow measurement (TTFM). HAV patency was assessed by computed tomography angiography (CTA) at 1, 3 and 6 months, and confirmed by left heart catheterization at the 6 month study endpoint. Explanted tissues were processed for histological analysis of host cellular repopulation and HAV remodeling. Results: Three animals were successfully bypassed with a 3.5 mm HAV as aorta-RCA CABG conduits with resulting TTFM blood flow rates of 22 ± 7.7 mL/min. CTA at 1, 3 and 6 months demonstrated patency of the HAV with no significant stenosis or dilatation. There were no HAV related adverse events for the duration of the study. Histological staining of 6 month explanted tissues showed recellularization and remodeling of the HAV with a microcapillary-containing neo-adventitial layer, alpha smooth muscle actin expressing cells within the HAV wall, and endothelialization of the HAV lumen. Conclusion: A small diameter, readily available HAV was successfully implanted in a primate model of CABG and remained patent up to 6 months with no evidence of dilatation. In addition, the HAVs were thoroughly recellularized and remodeled by host cells. These bioengineered vessels may prove to be durable long-term conduit options in CABG.
Abstract 10852: Stable versus Dynamic Cardiac Symptom Characteristics Are Associated With Adverse Outcomes Among Individuals Transported by Ambulance for Suspected Acute Coronary Syndrome
Authors: Jessica K Zegre-Hemsey, Jamie Crandell, Wayne D Rosamond, Eugenia Wong, Kevin Chronowski, Alec Tolentino, Kyle Ronn, Noah Steege, Michele M Pelter, Salah S Al-Zaiti, Stephanie Frisch, Victoria V Dickson, Holli A Devon
Journal: Circulation (2022)

Introduction: Acute coronary syndrome (ACS) is a potential life-threatening emergency; therefore, rapid diagnosis and life-saving reperfusion therapies are essential to prevent adverse outcomes. Patients with suspected ACS experience an array of symptoms, which cause patients to seek care (9-1-1 or self-transport) to the emergency department [ED]). Little is known, however, about the prognostic value of symptom characteristics experienced in the very early period of evolving ACS and its impact on adverse patient outcomes. The purpose of this study was to determine if early symptom changes reported in the prehospital period are associated with adverse outcomes. Methods Adults &gt; 21 years of age with non-traumatic chest pain and/or anginal equivalent symptoms transported by ambulance were included. Cardiac symptoms were measured prospectively with the ACS Symptom Checklist, a validated 13-item tool that takes approximately one-minute to complete. Trained EMS personnel administered the ACS Symptom Checklist during ambulance transport (T1) and research specialists measured symptoms again in the ED (T2), after acute triage care was completed. Symptom changes were categorized as an increase, decrease, or both from T1 to T2. Changes in symptoms between T1 and T2 were defined as stable (0-3 symptoms) or dynamic ( &gt; 4 symptoms). Adverse hospital outcomes included death, reinfarction, and/or new onset heart failure. Results To date, a total of 280 patients presenting to the ED by ambulance with suspected ACS have been enrolled (mean age 60.1 + 15.5 years; 51.2% female; 14.3% final diagnosis of ACS). Of 255(91.1%) patients with complete data, 143(51.1%) experienced stable symptoms and 112(40%) experienced dynamic symptoms. Patients with stable changes had significantly higher rates of adverse outcomes compared to patients with dynamic changes (11.9 versus 2.9%, p=0.007). Patients reporting shortness of breath at T1 or T2 were over 4 times likely to experience an adverse event (p=0.003, p=0007). Conclusions Patients with suspected ACS who have stable symptom changes were more likely to have an adverse hospital outcome. The underlying mechanism of plaque rupture in ACS may account for these differences in symptom characteristics but needs further study.
Abstract 10875: Metabolic Reprogramming of the Failing Fetal Heart in Twin-Twin Transfusion Syndrome
Authors: Jacqueline G Parchem, Huihui Fan, Lovepreet K Mann, Qiuying Chen, Jong Hak Won, Steven S Gross, Zhongming Zhao, Heinrich Taegtmeyer, Ramesha Papanna
Journal: Circulation (2022)

Adult heart failure is associated with reactivation of the fetal metabolic program, including impaired mitochondrial oxidative phosphorylation and a shift toward glycolysis. In the fetus, the metabolic response to cardiac stress is less clear. We used twin-twin transfusion syndrome (TTTS) as a model to uncover metabolic adaptations of the fetus to cardiovascular stress. TTTS is a unique complication that occurs in monochorionic-diamniotic twins (one placenta, two amniotic sacs) when unequal blood flow between twins within the shared placenta is the set up for donor-recipient physiology (Fig 1a). This circulatory imbalance is detected by sonographic signs of donor hypovolemia and recipient hypervolemia. We analyzed second trimester amniotic fluid to identify alterations in metabolism of TTTS recipient twins (n=22) vs. singleton controls (n=10) using untargeted metabolomics (LC/MS). All TTTS cases were severe (stage III; abnormal Dopplers indicating increased afterload and/or right heart failure). Due to dilution of amniotic fluid molecules in TTTS, data for each sample was normalized to protein concentration. Evaluation of differential metabolites in TTTS cases revealed two distinct clusters of disease (Fig. 1b). Compared with TTTS cluster 1 and controls, cluster 2 showed significantly increased lactate and alanine production, and evidence of redox stress (Fig. 1c). No differences in clinical characteristics or outcomes were observed between TTTS cluster 1 vs. 2 (maternal age, gestational age, fetal sex, disease severity, preterm birth, and perinatal death). Our findings reveal subclinical heterogeneity of stage III TTTS and suggest that some fetuses undergo metabolic reprogramming under conditions of cardiac stress, shifting even further toward energy-efficient glucose utilization. These differences in fetal response may represent different points along the same spectrum vs. inherent differences in the ability of fetuses to adapt to stress.
Abstract 10986: SGK1 Inhibition Attenuated the Action Potential Duration In-Patient and Genotype-Specific Re-Engineered Heart Cells With Congenital Long QT Syndrome
Authors: David J Tester, Saumya Das, Maengjo Kim, Sabindra Pradhananga, Samantha K Hamrick, Dinesh Srinivasan, Philip Sager, Michael J Ackerman
Journal: Circulation (2022)

Background: Long QT syndrome (LQTS) often stems from pathogenic variants in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3) and is characterized cellularly by prolongation of the cardiac action potential duration (APD). We have shown that inhibition of serum and glucocorticoid regulated kinase-1 (SGK1) reduces I NaL and is proposed as a novel therapeutic strategy for LQT3. Objective: To test the efficacy of a potent and selective SGK1 inhibitor (SGK1-I) in human cardiomyocyte models of LQT1, LQT2, and LQT3. Methods: Induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) were generated from patients with either LQT1, LQT2, or LQT3. The mexiletine (MEX)-sensitive SCN5A-P1332L iPSC-CMs were tested initially. A CRISPR/Cas9 P1332L variant-corrected isogenic control (IC) was used as a control. The SGK1-I’s therapeutic efficacy was compared to MEX and to a commercially available SGK1 inhibitor (EMD638683). The novel SGK-I was then tested for APD shortening in SCN5A-R1623Q, KCNH2-G604S and KCNQ1-V254M iPSC-CMs. The APD90 values were recorded 4 hours after treatment using FluoVolt. Results: The APD90 was significantly prolonged in SCN5A-P1332L iPSC-CMs compared to its IC (646 ± 7 ms vs 482 ± 23 ms, p&lt;0.0001). MEX shortened the average APD90 to 560 ± 7 ms (52% attenuation). Interestingly, SGK1-I significantly shortened the APD to 518 ± 5 ms (78% attenuation) but did not further shorten the APD in the IC. SGK1-I also shortened the APD90 of the SCN5A-R1623Q iPSC-CMs from 753 ± 8 ms to 475 ± 19 ms compared to 558 ± 19 ms with MEX. The SGK1-I shortened the APD90 in KCNH2-G604S (666 ± 10ms to 574 ± 18ms for SGK1-I versus 538 ± 15 ms after MEX). EMD had limited APD shortening effects in SCN5A and KCNH2 iPSC-CMs. Interestingly, while neither MEX nor EMD reduced the APD90 in the KCNQ1-V254M iPSC-CMs, the novel SGK1-I reduced the APD90 from 544 ± 10 ms to 475 ± 11ms (p=0.0004). Conclusions: Therapeutically inhibiting SGK1 effectively shortens the cardiomyocyte APD in human heart cell models of the 3 major LQTS genotypes. The novel SGK1-I normalized the pathological APD prolongation almost fully (&gt; 70%) in the patient-derived SCN5A-P1332L iPSC-CM model. These pre-clinical data support further development of SGK1-I as a novel, first-in-class therapy for patients with congenital LQTS.
Abstract 11038: Clinical Characteristics and Outcomes of High-Cost Pediatric Heart Transplant Hospitalizations in the United States
Authors: Matthew J O'Connor, Jonathan Edelson, Carol Wittlieb-Weber, Kimberly Y Lin, Jonathan Edwards, Joseph Rossano, Katsuhide Maeda, James W Gaynor, Danielle Burstein
Journal: Circulation (2022)

Introduction: Pediatric heart transplantation (HT) is resource-intensive, with the HT hospitalization being a major driver of costs. We sought to determine the characteristics and outcomes of patients whose HT hospital admissions incur high costs. Methods: The Pediatric Health Information System database was queried for pediatric (&lt;18 y) hospital admissions between 1/1/2008 and 12/31/2021 in which HT was performed. High-cost HT admission was defined as ≥95 th percentile of cost for all HT admissions during the study period. Costs were standardized across centers using a cost-to-charge ratio; all cost values (in US dollars) were indexed to the 2020 US Consumer Price Index. The primary outcome was mortality during the index HT admission. Clinical characteristics and outcomes were compared between high-cost HT admissions and lower-cost HT admissions (&lt;95 th cost percentile) using logistic regression. Results: A total of 4352 pediatric HTs were identified; for the entire cohort, median HT admission cost was $501,535 (IQR $270,291 - $902,302). Within the high-cost group (N = 217), HT admission costs ranged from $1,971,069 - $44,500,000; the majority (N = 195) had costs between $2 million and $5 million. High-cost admissions accounted for 23% of costs within the entire cohort. Median length of stay in the high-cost group was 247d (IQR 160d-342d) and 59d (IQR 24d-115d) in the lower-cost group (P&lt;0.001). High-cost HT admissions increased over time (2.9% of admissions in 2008; 5.5% in 2021, P&lt;0.001). Patients with high-cost HT admissions were younger (1y vs 6y, P&lt;0.001), more likely to have single ventricle congenital heart disease (42.4% vs 28.9%, P&lt;0.001), undergo ECMO (55.3% vs 19.3%) and/or VAD (37.3% vs 16.2%, P&lt;0.001 for both), and receive dialysis (13.8% vs 3.6%, P&lt;0.001). Hospital mortality was higher in high-cost HT patients (22.6% vs 4.2%, P&lt;0.001); this relationship persisted after adjusting for clinical and center characteristics (OR 7.2, 95% CI 4.97 - 10.57, P&lt;0.001). Conclusions: High-cost admissions for pediatric HT contribute disproportionately to overall hospital mortality and cost after HT, and are associated with high resource utilization. These findings highlight opportunities to improve outcomes in this growing and high-risk population.
Abstract 10060: Racial Differences in Outcomes of Hypertensive Crisis in Women With History of Preeclampsia: A National Sample Study
Authors: Moiz Ehtesham, Arshan Khan, Muhammad Asim Shabbir
Journal: Circulation (2022)

Objective: Preeclampsia has been shown to put women at an increased risk of developing hypertension later in life. We aimed to determine racial differences in in-hospital outcomes of hypertensive crisis in women with history of preeclampsia in the United States. Methods: The national inpatient sample was retrospectively studied from 2012-2019 to identify hospitalizations for hypertensive crisis aged &gt;18. We further identified history of preeclampsia within each admission using ICD-10 codes. The primary outcome was hospital length of stay (LOS) and inpatient mortality rate. Secondary outcomes were chosen as a 3-point composite development of stroke, myocardial infarction (MI) or congestive heart failure (CHF). Demographic (age, sex, race) information was also recorded. Caucasian patients were chosen as baseline reference to compare other ethnicities with. Data was analyzed with STATA 16.0, and adjusted odds ratios (AOR) were calculated using multivariate logistic regression. Results: There were 531,432 hospitalizations for hypertensive crisis, out of which 11% (58,457) had history of preeclampsia. 65% of this subset was Caucasian, 21% were African American (AA) and 11% Hispanic. Inpatient mortality rate was higher in Hispanic patients with preeclampsia vs Caucasians [6.2% vs 4.3%; AOR: 1.56 (1.49 – 1.61, p&lt;0.001)]. AA patients had a longer LOS vs Caucasians [5.5 vs 3.2; AOR: 1.21 (1.19 – 1.25, p&lt;0.001)]. There was no significant difference in LOS in Hispanic patients (p=0.08). Hispanic women had increased odds of developing stroke while inpatient compared to their Caucasian counterparts (AOR: 2.31, p&lt;0.001). There was no significant difference in development of MI amongst the races (p=0.09). However, AA women with history of preeclampsia were more likely to develop CHF compared to Caucasians (AOR: 1.92, p&lt;0.001). Conclusion: Hispanic women with history of preeclampsia have higher mortality rate and incidence of stroke when admitted with hypertensive crisis. Similarly, African American women with preeclampsia have longer hospital stay when admitted with hypertensive crisis. Further research is needed to understand and alleviate these cardiovascular burdens in ethnic minorities.